Triple superior to quadruple combination ART for treatment-naïve people with HIV
A quadruple combination antiretroviral therapy (cART) demonstrates similar effects when compared to a triple cART in treatment-naïve people with HIV, according to the results of a systematic review and meta-analysis.
“This finding lends support to current guidelines recommending triple cART as first-line treatment, especially considering the financial and pill burden and consequent issues introduced by a fourth drug,” researchers said.
Randomized controlled trials (RCTs) were searched in PubMed, Embase, Central, Web of Science and the Cumulative Index to Nursing and Allied Health Literature from March 2001 to December 2016. PubMed and Embase were accessed again up to June 2018 for an updated search. Reference lists of eligible studies and related reviews were also searched.
RCTs that compared quadruple with triple cART in treatment-naïve people with HIV and evaluated at least one effectiveness or safety outcome were included. Outcomes of interest were as follows: HIV-1 RNA, CD3 T cell count, virological failure, new AIDS defining events, death and severe adverse effects. Random effects meta-analyses were performed.
Twelve RCTs, including 4,251 people with HIV, met the inclusion criteria. The effects of quadruple cART on all relevant effectiveness and safety outcomes were comparable with those of triple cART, with no point estimates favouring quadruple therapy. [BMJ 2019;366:l4179]
The risk ratio relative to the triple cART was 0.99 (95 percent CI, 0.93–1.05) for undetectable HIV-1 RNA, 1.00 (0.90–1.11) for virological failure, 1.17 (0.84–1.63) for new AIDS defining events, 1.23 (0.74–2.05) for death, and 1.09 (0.89–1.33) for severe adverse effects. The mean difference in CD4 T cell count increase was –19.55 cells/μL (–43.02 to 3.92) between the two treatment arms.
“In general, the results were similar, regardless of the specific regimens of combination antiretroviral therapies, and were robust in all subgroup and sensitivity analyses,” researchers said.
Subgroup analyses showed that different drug combinations would not necessarily result in a big difference between quadruple and triple cART even as their combinations could contribute to the effects of the two regimen types themselves. [BMJ 2002;324:757; Lancet HIV 2016;3:e510-e520]
Moreover, the addition of a fourth drug to first-line treatment increases financial and pill burden, potentially leading to a reduced medication adherence and, consequently, drug resistance and treatment failure. It may also limit drug options for second-line treatment and beyond, according to researchers. [Clin Infect Dis 2003;37:1112-1118; Infect Disord Drug Targets 2011;11:167-174]
It could be thus concluded that triple cART is superior to quadruple cART and that current guidelines recommending triple therapy as first-line treatment remain relevant, they added. [JAMA 2014;312:410-425; www.who.int/hiv/pub/arv/arv-2016/en/; www.eacsociety.org/guidelines/eacs-guidelines/eacs-guidelines.html; www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf]
“As the chance that quadruple cART turns out to be more favourable than triple cART is low, the idea of evidence-based research deserves more emphasis in proposing further trials on this topic,” researchers said. “However, this study does not exclude the possibility that quadruple cART would be better than triple ones when new classes of antiretroviral drugs are made available.”